|AFFILIATIONS||Professor of Vision Science and Optometry
Vision Science Program Chair
Intrinsic Protective Circuits in Ocular Inflammatory, Immune and Wound Healing Responses
Inflammation is a highly regulated and elegant response to injury, stress and infection. At any given time in life there are multiple sites of healthy and temporary inflammation that often go unnoticed in tissue/organs such as skin, gastrointestinal tract, mouth, eyes, blood vessels and lungs. More importantly, inflammation is essential to health and survival of all living organisms. Healthy inflammation protects a wound against invading bacteria/viruses, removes dead tissue and cells and regulates the repair of injured or stressed tissue. By design a healthy inflammatory response is beneficial, temporary, resolves naturally, and restores normal function of the afflicted tissue/organ.
Unfortunately, the complex regulation of healthy inflammation is in a precarious balance that can tip towards causing unwanted tissue damage and lead to abnormal or chronic inflammation. Diet, overall state of health, and environmental factors can tip healthy inflammation to an uncontrolled and disease causing inflammatory event. Dysregulated inflammation is now recognized as a major factor in the global disease burden and the cause of cardiovascular diseases (atherosclerosis, heart attacks, stroke), asthma, arthritis, allergies, cancer and blindness. Traditionally therapeutic approaches have focused simply on inhibiting pathways that initiate or amplify inflammation, which can lead to significant and potentially dangerous side effects.
Research efforts in the Gronert Laboratory are part of a new paradigm that has established lipid circuits as critical regulators for the successful execution of a normal healthy inflammatory response. These lipid circuits are essential components of a “resolution program” that helps remodel injured tissue, removes spent white blood cells and naturally terminates the inflammatory response. Intense research efforts in the last few years by a small group of research teams around the world has spurred enormous interest in these resident protective lipid circuits as a major target for the development of much needed novel drugs for the treatment of inflammatory diseases. Our research team is focused on elucidating the role of these endogenous protective circuits in inflammation and wound healing and to define their critical regulation by dietary omega-3 PUFA (fish oils). Karsten Gronert was a member of the research team that discovered that fish oils (omega-3 PUFA) are converted to specific protective lipid signals in the body. These findings have provided a molecular mechanism for the remarkable beneficial actions of dietary omega-3 PUFA, which has eluded scientist for decades.
Research project in the laboratory employ innovative approaches and state-of-the art technology to discover and define the endogenous role of protective lipid circuits in the body and cells with the long-term goal of identify novel drug targets or treatment options for inflammatory diseases. Our main research project is sponsored by the National Eye Institute and is focused on elucidating the formation and molecular mechanisms of protective lipid signals in the sequelae of ocular injury. Our research efforts in the last few years have uncovered that protective lipid mediator circuits and “resolution programs” are highly and selectively expressed in the delicate visual axis. Current efforts are aimed at defining the role and regulation of these intrinsic protective pathways and “resolution program” in normal ocular physiology and inflammatory diseases. In addition, the Gronert laboratory collaborates with leading research teams at Children’s Hospital/Harvard Medical School, Charité University Clinic in Germany and the National Institute for Digestive and Diabetes and Kidney Disease to define the role and molecular mechanisms of action for omega-3 PUFA circuits in healthy humans and human patients with inflammatory diseases as well as in experiments that model the leading causes of blindness.